The Yale University, W.M. Keck Biotechnology Resource Laboratory's MS &Proteomics Core has developed a state-of-the-art proteomic technology to maximally support "Bench-to-Bedside Research". This new service entitled targeted proteomics utilizes an emerging mass spectrometry based paradigm for validating, quantitating, and potentially generating a new diagnostic tool for identification and confirmation of protein biomarkers from clinical samples. Due to rapid acceptance of this technology from Yale investigators, we are requesting funding for a hybrid triple quadrupole-linear ion trap mass spectrometer, 5500 QTRAP manufactured by Applied Biosystems, which would be devoted to meeting the very rapidly increasing need for quantifying the levels of multiple preselected proteins. In addition, we are also requesting an automated sample injector and HPLC system, the nanoACQUITY UPLC manufactured by Waters Corporation, that is needed to interface with the MS and that will provide automated sample handing and peptide separation prior to MS analysis, thus enabling continuous 24/7 analysis of very complex samples. When the requested instrumentation is combined with our in-house developed targeted proteomic service, the resulting platform will enable us to expand targeted proteomics and support the 29 NIH-funded projects directed by 21 investigators in this proposal. These investigators propose to use our targeted proteomic service to advance diverse biomedical research on: Cancer (angiogenesis, papillomaviruses, and Melanoma), Diabetes, Drug Addiction, Neuronal Development, Cardiovascular disease, Autism, Influenza, Synaptic Transmission, Chronic Kidney Disease, Drug Addiction, Spitzoid neoplasms, and Down syndrome. Two of the major users, Richard Lifton (NHLBI Proteomics Center) and Angus Nairn (NIDA Neuroproteomics Center), will collaborate with our center to pursue their research applications in renal disease and in drug addiction and depression while also collaborating on biotechnology research directed at further advancing our highly promising targeted proteomic technologies. This effort will then assist in rapidly developing new targeted proteomic services that will be made available to all other research contributors and users of the Keck Lab. Progress in this research will advance knowledge of how best to understand, prevent, and treat human diseases. The requested 5500 QTRAP mass spectrometer (MS) would be unique to Yale University, and would be available to other interested investigators due to its placement in a core facility that accepts samples from across the U.S. and (when needed to keep its instrumentation operating at capacity) from around the world. Thus, the 5500 QTRAP MS would significantly contribute to biomedical research at Yale University and beyond. PUBLIC HEALTH RELEVANCE: If this grant is funded, the requested 5500 QTRAP mass spectrometer would make a unique and substantial contribution to biomedical research that would extend to investigators studying fundamental mechanisms of many diseases, including diabetes, substance abuse, influenza, cancer, renal diseases, autism, hypertension, and Down syndrome.